Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization

An Liu; Zikai Zhou; Rui Dang; Yuehua Zhu; Junxia Qi; Guiqin He; Celeste Leung; Daniel Pak; Zhengping Jia; Wei Xie

doi:10.1083/jcb.201509023

Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization

J Cell Biol. 2016 Feb 15;212(4):449-63. doi: 10.1083/jcb.201509023.

Authors

An Liu¹, Zikai Zhou², Rui Dang¹, Yuehua Zhu¹, Junxia Qi¹, Guiqin He¹, Celeste Leung³, Daniel Pak⁴, Zhengping Jia⁵, Wei Xie⁶

Affiliations

¹ The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China.
² The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China Institute of Life Sciences, The Collaborative Innovation Center for Brain Science, Southeast University, Nanjing 210096, China.
³ Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
⁴ Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC 20007.
⁵ Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada zhengping.jia@sickkids.ca wei.xie@seu.edu.cn.
⁶ The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China Institute of Life Sciences, The Collaborative Innovation Center for Brain Science, Southeast University, Nanjing 210096, China zhengping.jia@sickkids.ca wei.xie@seu.edu.cn.

Abstract

Neuroligin (NLG) 1 is important for synapse development and function, but the underlying mechanisms remain unclear. It is known that at least some aspects of NLG1 function are independent of the presynaptic neurexin, suggesting that the C-terminal domain (CTD) of NLG1 may be sufficient for synaptic regulation. In addition, NLG1 is subjected to activity-dependent proteolytic cleavage, generating a cytosolic CTD fragment, but the significance of this process remains unknown. In this study, we show that the CTD of NLG1 is sufficient to (a) enhance spine and synapse number, (b) modulate synaptic plasticity, and (c) exert these effects via its interaction with spine-associated Rap guanosine triphosphatase-activating protein and subsequent activation of LIM-domain protein kinase 1/cofilin-mediated actin reorganization. Our results provide a novel postsynaptic mechanism by which NLG1 regulates synapse development and function.

MeSH terms

Actin Cytoskeleton / enzymology*
Actin Depolymerizing Factors / metabolism*
Animals
Cell Adhesion Molecules, Neuronal / deficiency
Cell Adhesion Molecules, Neuronal / genetics
Cell Adhesion Molecules, Neuronal / metabolism*
Cerebral Cortex / cytology
Cerebral Cortex / enzymology*
Dendritic Spines / enzymology*
GTPase-Activating Proteins / metabolism
Genotype
HEK293 Cells
Hippocampus / cytology
Hippocampus / enzymology*
Humans
In Vitro Techniques
Lim Kinases / deficiency
Lim Kinases / genetics
Lim Kinases / metabolism*
Mice, Knockout
Neuronal Plasticity*
Phenotype
Phosphorylation
Protein Binding
Protein Interaction Domains and Motifs
RNA Interference
Signal Transduction
Synapses / enzymology*
Time Factors
Transfection
rap1 GTP-Binding Proteins / metabolism

Substances

Actin Depolymerizing Factors
Cell Adhesion Molecules, Neuronal
GTPase-Activating Proteins
Sipa1l1 protein, mouse
neuroligin 1
Lim Kinases
Limk1 protein, mouse
Limk2 protein, mouse
rap1 GTP-Binding Proteins